PMID- 1325687
OWN - NLM
STAT- MEDLINE
DCOM- 19921007
LR  - 20190819
IS  - 0041-0101 (Print)
IS  - 0041-0101 (Linking)
VI  - 30
IP  - 5-6
DP  - 1992 May-Jun
TI  - Actions of 6-epitetrodotoxin and 11-deoxytetrodotoxin on the frog skeletal muscle 
      fiber.
PG  - 635-43
AB  - 6-Epitetrodotoxin (6-epiTTX) and 11-deoxytetrodotoxin (11-deoxyTTX), isolated 
      from an Okinawan newt, Cynops ensicauda, were tested for sodium-channel blocking 
      effects on the voltage-clamped frog skeletal muscle fiber. In 6-epiTTX, the C-6 
      -OH is in an epimeric position; in 11-deoxyTTX, C-11 has a methyl in place of a 
      hydroxymethyl group. At pH 7.25, the ED50s for reducing INa are: 4.1 nM (TTX), 96 
      nM (6-epiTTX), and 445 nM (11-deoxyTTX). In each analogue, the lowered potency 
      can be attributed energetically to the loss of a hydrogen bond. By 
      complementarity, in the sodium-channel receptor for TTX, there must be a 
      hydrogen-acceptor group for the C-6 -OH, and another for the C-11 -OH. Therefore, 
      the TTX molecule is bound to the receptor through an ion-pair (for the 
      guanidinium), and five hydrogen bonds, one each for the -OH on C-9, C-10, C-4, 
      and, as now identified, for C-6 and C-11. Considering the three-dimensional 
      structure of the toxin molecules, these binding sites must be located in a fold 
      or a crevice of the channel protein. If glutamate 387 of rat brain sodium channel 
      II is the ion-pairing site for the guanidinium group, then the carbonyl oxygen of 
      asparagine 388 is the hydrogen acceptor for the C-9 and C-10 -OHs.
FAU - Yang, L
AU  - Yang L
AD  - Department of Pharmacology, State University of New York, Brooklyn 11203.
FAU - Kao, C Y
AU  - Kao CY
FAU - Yasumoto, T
AU  - Yasumoto T
LA  - eng
GR  - NS14551/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Toxicon
JT  - Toxicon : official journal of the International Society on Toxinology
JID - 1307333
RN  - 0 (Potassium Channels)
RN  - 0 (Sodium Channels)
RN  - 112318-40-8 (6-epitetrodotoxin)
RN  - 113564-23-1 (11-deoxytetrodotoxin)
RN  - 4368-28-9 (Tetrodotoxin)
SB  - IM
MH  - Animals
MH  - In Vitro Techniques
MH  - Molecular Structure
MH  - Muscles/*drug effects
MH  - Potassium Channels/drug effects
MH  - Rana temporaria
MH  - Sodium Channels/*drug effects
MH  - Tetrodotoxin/*pharmacology
EDAT- 1992/05/01 00:00
MHDA- 1992/05/01 00:01
CRDT- 1992/05/01 00:00
PHST- 1992/05/01 00:00 [pubmed]
PHST- 1992/05/01 00:01 [medline]
PHST- 1992/05/01 00:00 [entrez]
AID - 10.1016/0041-0101(92)90857-2 [doi]
PST - ppublish
SO  - Toxicon. 1992 May-Jun;30(5-6):635-43. doi: 10.1016/0041-0101(92)90857-2.